The Role of Cystathionine-γ-lyase in Blunt Chest Trauma in Cigarette Smoke Exposed Mice

Clair Hartmann, Sebastian Hafner, Angelika Scheuerle, Peter Möller, Markus Huber-Lang, Birgit Jung, Benedikt Nubaum, Oscar McCook, Michael Gröger, Florian Wagner, Sandra Weber, Bettina Stahl, Enrico Calzia, Michael Georgieff, Csaba Szabo, Rui Wang, Peter Radermacher, Katja Wagner

    Research output: Contribution to journalArticle

    4 Scopus citations

    Abstract

    ABSTRACT: Pre-traumatic cigarette smoke (CS) exposure aggravates post-traumatic acute lung injury (ALI). Cystathionine-γ-lyase (CSE) protects against ALI and CS exposure-induced chronic obstructive lung disease (COPD). Therefore, we tested the hypothesis whether genetic CSE knockout (CSE) would aggravate post-traumatic ALI after CS exposure. After 3–4 weeks of CS exposure, anesthetized wild type (WT) and CSE mice underwent blunt chest trauma, surgical instrumentation and 4?hours of lung-protective mechanical ventilation. We measured hemodynamics, lung mechanics, gas exchange, metabolism and acid-base status together with blood and tissue cytokine and chemokine levels, tissue expression of mediator proteins, parameters of oxidative and nitrosative stress, and histology. CSE mice without CS exposure, showed higher cytokine and chemokine levels, and this was further enhanced by CS exposure, particularly in males. CS exposure in WT mice aggravated post-traumatic alveolar membrane thickening, dystelectasis and inflammatory cell accumulation, which was associated with higher thoracopulmonary compliance. Pre-traumatic CS exposure in CSE mice produced a similar response, except for less alveolar membrane thickening, most likely due to lung hyperinflation. CS-exposed WT mice showed the most pronounced metabolic acidosis, while CS exposure in CSE mice resulted in the lowest blood glucose levels. Urinary output and anesthesia rate were highest in male CS-exposure CSE animals. In conclusion, in murine acute-on-chronic pulmonary disease, CSE knockout aggravated post-traumatic inflammation, which was further worsened upon pre-traumatic CS exposure, and this effect was particularly pronounced in males. Hence, maintaining CSE expression is critically important for stress adaptation during ALI and CS-induced COPD, most likely in a gender-dependent manner.

    Original languageEnglish (US)
    JournalShock
    DOIs
    StateAccepted/In press - Sep 28 2016

    ASJC Scopus subject areas

    • Emergency Medicine
    • Critical Care and Intensive Care Medicine

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  • Cite this

    Hartmann, C., Hafner, S., Scheuerle, A., Möller, P., Huber-Lang, M., Jung, B., Nubaum, B., McCook, O., Gröger, M., Wagner, F., Weber, S., Stahl, B., Calzia, E., Georgieff, M., Szabo, C., Wang, R., Radermacher, P., & Wagner, K. (Accepted/In press). The Role of Cystathionine-γ-lyase in Blunt Chest Trauma in Cigarette Smoke Exposed Mice. Shock. https://doi.org/10.1097/SHK.0000000000000746